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PubMed1983

Human chromosomal polymorphism. VII. The distribution of chromosomal Q-polymorphic bands in different human populations.

The distribution of chromosomal Q-polymorphic bands was studied in different human populations. The populations studied showed no differences in the relative amount of Q bands in all the 12 polymorphic loci of seven autosomes, but interpopulation differences did exist in the absolute amount of Q bands in all the 12 potentially polymorphic loci of seven autosomes, these differences consisting of uniform increases or decreases in this absolute amount. Comparisons of the mean number of Q-heterochromatin bands with fluorescence levels 4 and 5 per individual showed a consistent prevalence of this quantitative parameter of chromosomal Q polymorphism in females as compared to males in all the national groups. It is suggested that there is some dosage compensation of chromosomal Q-heterochromatin material in females due to the absence of a chromosome in their genome, which is able to "compensate" for the large Q band in chromosome Y which is present only in the karyotype of males.

Africa↗

PubMed1987

Polymorphisms within the HLA-DRw6 haplotype. III. DQ alpha and DQ beta polymorphism associated with HLA-D.

We have studied HLA-DQ encoded antigens from HLA-DRw6 homozygous cells and analyzed the DQ region at the DNA level. HLA-DQ molecules were isolated from EBV transformed B-cell lines and analyzed for DQ alpha and DQ beta polymorphism. From the same set of cells, DNA was isolated and analyzed for RFLP. Polymorphism could be detected by both techniques, i.e., on the protein level and on the DNA. The variation in pI of the DQ alpha and beta chains correlated with the polymorphism as detected by HTC typing, as did the variation in molecular weight of the bands hybridizing to DQ specific cDNA probes; identical patterns were detected for cells of one HLA-D specificity and different patterns for different HLA-D types. Additionally, DQ reactive PLT reagents were raised against DRw6 positive cells. Panel studies revealed that these DQ reactive proliferative T cells can discriminate between the polymorphic DQ antigens on cells with different HLA-D specificities.

Antibodies, Monoclonal↗

PubMed2001

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction.

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.

Aged↗

PubMed2001

The -629C>A polymorphism in the CETP gene does not explain the association of TaqIB polymorphism with risk and age of myocardial infarction in Icelandic men.

The aim of this study was to examine whether the well-established effect of the common TaqIB polymorphism in intron 1 of the gene for cholesterol ester transfer protein (CETP) on high density lipoprotein cholesterol (HDL-C) concentration and increased risk of myocardial infarction (MI), could be explained by the recently identified -629C>A functional polymorphism in the promoter. Non-fatal MI cases (388 male) and a control group of 794 healthy men were recruited from the 30 year long prospective Reykjavik Study. In the healthy men the frequency of the TaqIB B2 allele was 0.47 (95% CI: 0.44-0.50) and there was a strong allelic association with the -629A allele (D=-0.21, P<0.0001), which had a frequency of 0.52 (95% CI: 0.49-0.56). B2B2 homozygotes displayed 15% higher HDL-C levels than subjects homozygous for the B1 allele (P<0.0001). Homozygotes for the -629A allele displayed 14% higher HDL-C concentrations than subjects homozygous for the -629C allele (P<0.0001). The frequencies of the alleles associated with lower HDL-C were significantly higher in cases compared with controls, 0.59 versus 0.53 (TaqIB B1) and 0.52 versus 0.48 (-629 C) respectively (P<0.05 for both). There was a significantly higher risk for MI in B1B1 homozygotes (OR=1.44, 95% CI: 1.10-1.87, P<0.01), compared to the other genotypes combined. This was not observed for the CC homozygotes (OR=1.16, 95% CI: 0.87-1.54). In addition, homozygotes for the TaqI B2 allele experienced a first MI 2 years later than men with other genotypes, 59 versus 61 years (P<0.05). This effect was not seen for the promoter polymorphism. These results strongly confirm the role of the CETP gene and the TaqIB variant as a risk factor for MI and suggest that another functional polymorphism is yet to be discovered in the CETP gene, that will explain the effect on MI associated with TaqIB observed in this study.

Aged↗

PubMed2002

Effects of coagulation Factor VII polymorphisms on the coronary artery disease in Japanese: Factor VII polymorphism and coronary disease.

We investigated the relationships among Factor VII coagulant activity (FVIIc), genetic polymorphisms of Factor VII (FVII) and coronary artery disease (CAD) in 380 unrelated Japanese individuals (mean 64 years) who underwent coronary angiography and whose cholesterol levels were within normal range. CAD subjects were defined as those in whom one of the three major coronary arteries showed >50% narrowing after nitroglycerin administration. FVIIc was measured and the following polymorphisms of FVII were determined: R353Q polymorphism (M1, M2 alleles), -323 0/10 bp polymorphism (0, 10 alleles), hypervariable region 4 of intron 7 (HVR4; H5, H6, H7 alleles). FVIIc was slightly lower in M1M2/M2M2 than M1M1 (89.5+/-8.9%, 93.4+/-17.8%). Those with M2 and/or 10 allele have less chance of developing CAD (M2: OR 0.36, 95% CI 0.18-0.69, 10: OR 0.50, 95% CI 0.26-0.97). However, both alleles did not associate with myocardial infarction (MI). HVR4 was unrelated with CAD, nor with MI. In conclusion, M2 and/or 10 allele has protective effects on the developing CAD in individuals with a normal cholesterol level.

Aged↗

PubMed2002

Monoamine oxidase: A gene polymorphism, tryptophan hydroxylase gene polymorphism and antidepressant response to fluvoxamine in Japanese patients with major depressive disorder.

Monoamine oxidase A (MAOA) and tryptophan hydroxylase (TPH) are the staple enzymes in the metabolism of serotonin (5-HT). The genetic polymorphisms of these two enzymes might individually alter the production, release, reuptake or degradation of 5-HT during the treatment of selective serotonin reuptake inhibitors (SSRIs), leading to the individual differences in the antidepressant effects of SSRIs. The authors investigated whether a functional polymorphism in the MAOA gene promoter (MAOA-VNTR) and a TPH gene polymorphism in intron 7 (TPH-A218C) were associated with the antidepressant response to fluvoxamine in 66 Japanese patients with major depressive disorder during a 6-week study with a specific dosage plan. Fifty-four patients completed the study. The present study fails to demonstrate that the genetic polymorphisms of MAOA-VNTR and TPH-A218C affect the antidepressant effect of fluvoxamine in Japanese patients with major depressive disorder.

Adult↗

PubMed2003

Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T Kozak (GP Ibalpha) polymorphisms.

OBJECTIVES: We investigated whether three platelet gene polymorphisms, Pl(A1/A2), C807T, and C-5T Kozak (encoding, respectively, for platelet membrane glycoproteins (GP) IIIa, GP Ia/IIa, GP Ibalpha), could contribute to the resistance to a low dose of aspirin (160 mg/day). BACKGROUND: Aspirin antiplatelet effect is not uniform in all patients, and the mechanism by which some patients are in vitro resistant to aspirin remains to be determined. However, it has been suggested that polymorphisms of platelet membrane glycoproteins might contribute to aspirin resistance. METHODS: Ninety-eight patients on aspirin (160 mg/day) for at least one month were enrolled. Aspirin resistance was measured by the platelet function analyzer (PFA)-100 analyzer; genotyping of the three polymorphisms was performed using a polymerase chain reaction-based restriction fragment-length polymorphism analysis. RESULTS: Using a collagen/epinephrine-coated cartridge on the PFA-100, the prevalence of aspirin resistance was 29.6% (n = 29). Aspirin-resistant patients were significantly more often Pl(A1/A1) (86.2%; n = 25) than sensitive patients (59.4%; n = 41; p = 0.01). Of the 29 patients, 25 were reevaluated after having taken 300 mg/day aspirin for at least one month. Only 11 patients still have nonprolonged collagen epinephrine closure time, and these were all Pl(A1/A1). No relation was found between resistance status and C-5T Kozak or C807T genotypes. CONCLUSIONS: Platelets homozygous for the Pl(A1) allele appear to be less sensitive to inhibitory action of low-dose aspirin. This differential sensitivity to aspirin may have potential clinical implications whereby specific antiplatelet therapy may be best tailored according to the patient's Pl(A) genotype.

Aged↗

PubMed1998

A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter.

Several studies have shown an association between schizophrenia and the C allele of a T-C polymorphism at nucleotide 102 and the 5HT2A receptor gene. In the present study we observed this association in a sample of 63 parent/offspring trios where the proband received a diagnosis of DSM-III-R schizophrenia using TDT analysis (chi2 = 6.26, P= 0.006, chi2 = 9.00, P=0.001 when one affected offspring was selected at random from each family, suggesting that the results are due to association rather than linkage). There was no significant difference between the transmission of C102 from heterozygous fathers and mothers, which fails to support a role for genomic imprinting in this effect. T102C does not result in an alteration of the amino acid sequence of the protein. We therefore screened the promoter of 5HT2A for polymorphisms using single-strand confirmation polymorphism analysis. An A-G polymorphism at -1438 that creates an HpaII restriction site was identified. This was found to be in complete linkage disequilibrium with T102C and is hence a candidate for the pathogenic variant in schizophrenia. Functional analysis of A-1438G using luciferase assay demonstrated significant basal promoter activity in 5HT2A expressing HeLa cells by both the A and G variants. However, comparison of the A and G variants showed no significant differences in basal activity nor when promoter activity was induced by cAMP and protein kinase C-dependent mechanisms.

Adult↗

PubMed1987

Human complement C3b/C4b receptor (CR1) mRNA polymorphism that correlates with the CR1 allelic molecular weight polymorphism.

The human C3b/C4b receptor (CR1) is a Mr approximately equal to 200,000 single-chain integral membrane glycoprotein of human erythrocytes and leukocytes. It functions both as a receptor for C3b- and C4b-coated ligands and as a regulator of complement activation. Prior structural studies have defined an unusual molecular weight allelic polymorphism in which the allelic products differ in molecular weight by as much as 90,000. On peripheral blood cells there is codominant expression of CR1 gene products of Mr 190,000 (A), 220,000 (B), 160,000 (C), and 250,000 (D). Results of prior biosynthetic and tryptic peptide mapping experiments have suggested that the most likely basis for the allelic molecular weight differences is at the polypeptide level. In order to define further the molecular basis for these molecular weight differences, human CR1 was purified to homogeneity, tryptic peptide fragments were isolated by HPLC and sequenced, oligonucleotide probes were prepared, and a CR1 cDNA was identified. A subclone of this CR1 cDNA was used as a probe of RNA blots of Epstein-Barr virus-transformed cell lines expressing the allelic variants. Each allelic variant encodes two distinct transcripts. A mRNA size polymorphism was identified that correlated with the gene product molecular weight polymorphism. This finding, in addition to a prior report of several homologous repeats in CR1, is consistent with the hypothesis that the molecular weight polymorphism is determined at the genomic level and may have been generated by unequal crossing-over.

Alleles↗

PubMed2000

Identification of the Hind III polymorphic site in the PAI-1 gene: analysis of the PAI-1 Hind III polymorphism by PCR.

The identification of the Hind III polymorphic site in the 3' end of the plasminogen activator inhibitor 1 (PAI-1) gene and a simple method to identify the Hind III polymorphism rapidly in the PAI-1 gene using PCR is described. The Hind III restriction site was identified by restriction site mapping and sequence analysis from a cosmid DNA clone. Genomic DNA was isolated from individual human umbilical cords and a 754-bp fragment of the human PAI-1 gene was amplified by PCR. Aliquots of the PCR products were digested with Hind III and analyzed by agarose gel electrophoresis. The presence of two fragments, 754 and 567 bp, was identified, and they were designated as 1/1 (750-bp band), 1/2 (754- and 567-bp bands), and 2/2 (567-bp band). The PCR method is considerably less time consuming than the conventional DNA genotyping using Southern blot analysis. To ensure that this new method identified the same PAI-1 genotypes as previously identified by Hind III restriction fragment length polymorphism (RFLP), samples were simultaneously genotyped by PCR and Southern blot analysis. Both methods identified the same Hind III genotypes in all the samples, confirming the reliability of this new PCR method for the rapid identification of the Hind III polymorphism in the human PAI-1 gene.

3' Untranslated Regions↗

PubMed1997

Polymorphism at beta 85 and not beta 86 of HLA-DR1 is predominantly responsible for restricting the nature of the anchor side chain: implication for concerted effects of class II MHC polymorphism.

The first hydrophobic pocket, P1, of class II MHC has been shown to be an important site of peptide anchoring. Two polymorphisms occur in this pocket in the human class II MHC beta chain at position 85 and 86. beta 85 is usually Val, occasionally Ala, whereas beta 86 can be Gly or Val. However, Ala85 is found only in conjunction with Val86. The independent effect of the polymorphism at these two positions on the binding of normal and substituted antigenic peptides has never been examined. To do so, three soluble HLA-DR1 variants that contain the naturally occurring combinations of these side chains at these two positions were generated and tested with a panel of influenza matrix peptides varying at anchor P1. DR1 alleles differing only at position 86 are very similar in the binding of a panel of antigenic peptide, indicating that beta 86 does not substantially influence the peptide binding of DR1. In contrast, DR1 varying only at position beta 85 differ in their binding of substituted peptides containing Ala, Tyr or Trp at the P1 anchor position. Thus, beta 85 shows the predominant effect on the P1 anchor side chain preference of the P1 pocket in DR1. This is in contrast to other HLA-DR alleles where beta 86 has been shown to control the nature of the P1 anchor. These previous data together with our own imply that the role of polymorphism in P1 may be influenced by the contextual framework of the remaining allelic polymorphism.

Alleles↗

PubMed1996

Failure to find associations of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia.

This study aimed to replicate positive associations between polymorphisms of the neurotrophin-3 gene and schizophrenia. The reported associations, which were the results of searching for mutations in the locus in schizophrenics under the hypothesis of neurodevelopmental etiology of schizophrenia, are that the states carrying the (CA)23 allele of the CA repeat in the first intron have a 2.56-fold increased risk of schizophrenia and those carrying the allele Glu-63 instead of Gly-63 have a 2.6-fold increased risk of schizophrenia with onset before 25 years and with duration of the illness of more than 10 years. We analyzed these polymorphisms in 80 schizophrenics with onset before 25 years of age and with duration of illness of more than 10 years and 80 age-matched psychosis-free controls. With our sample size, there was a 90% chance of detecting odds ratios observed in initial positive reports. We found similar allele and genotype frequencies of both polymorphisms between the schizophrenic and control groups. We failed to support associations between the polymorphisms of the neurotrophin-3 gene analyzed and schizophrenia.

Adult↗

PubMed1993

Double-strand DNA conformation polymorphisms as a source of highly polymorphic genetic markers.

The molecular basis for several apparent restriction fragment length polymorphisms of the porcine growth hormone gene was examined through DNA sequence analysis. Electrophoretic and sequence analysis suggest polymorphisms result from 1-3 base substitutions that affect double-strand DNA conformation and electrophoretic mobility. Two allelic forms of the porcine growth hormone 5' flank and four allelic forms of the second exon/intron region were identified. A marker system was developed which combined conformation polymorphisms with HaeII and DdeI RFLPs. Using this system, nine haplotypes were observed in samples from three US swine breeds. The data presented suggest that double-strand DNA conformation can be exploited in base substitution detection and development of highly polymorphic genetic marker systems.

Alleles↗

PubMed1993

Detection of highly polymorphic microsatellite loci in a species with little allozyme polymorphism.

Microsatellite loci are regions of DNA containing tandem repeats of a short sequence motif; they occur abundantly in all eukaryotic genomes and have been shown to be a rich source of highly polymorphic genetic markers in humans and other mammals. These loci are particularly suitable for population studies because they can be relatively easily scored using a combination of polymerase chain reaction (PCR) amplification of each locus followed by electrophoresis to separate alleles. This paper details a method for finding these loci in any species. This method demonstrates that trinucleotide microsatellite loci are abundant and highly polymorphic in the social wasp Polistes annularis, whereas allozyme electrophoresis reveals very little polymorphism. The first six loci examined were all polymorphic with a mean observed heterozygosity of 0.62; in comparison average heterozygosity of 33 allozymes was 0.035. We suggest that this method can be used to detect variation where other methods have failed, making it an ideal tool for population and conservation geneticists who must deal with populations lacking other types of genetic variability.

Alleles↗

PubMed1992

Detection of polymorphic loci in Arachis germplasm using random amplified polymorphic DNAs.

The development of easily scoreable genetic markers in Arachis will facilitate the introgression of desirable traits from wild species into adapted germplasm. We have used random amplified polymorphic DNAs (RAPDs) to identify polymorphic molecular markers in a range of wild and cultivated Arachis species. From a total of sixty 10-mer oligonucleotide primers, 49 polymorphic loci were identified between cultivated A. hypogaea type (TMV-2) and a synthetic amphidiploid (B x C)2 created from a A. batizocoi and A. chacoense cross. The inheritance of polymorphic markers, both in the amphidiploid and in the F1 progeny in a TMV-2 x (B x C)2 cross, has also been demonstrated. The potential exploitation of RAPD markers in groundnut improvement programs is discussed.

Arachis↗

PubMed1993

Application of the random amplified polymorphic DNA technique for the detection of polymorphism among wild and cultivated tetraploid wheats.

Development of a high-density genetic linkage map of cultivated wheats using conventional molecular markers has lagged behind the other major food crops such as rice and tomato because of the large genome size and limited levels of genetic polymorphisms. Recently, random amplified polymorphic DNAs (RAPDs) have been suggested to provide an alternative to visualize more polymorphism. For the construction of a genetic linkage map in tetraploid wheats, one can use a strategy of intersubspecific crosses between the most dissimilar wild and cultivated tetraploid wheats that are easy to hybridize and result in fertile progeny. An assessment of the level of RAPDs among different accessions and varieties of wild and cultivated tetraploid wheats is required to fulfill this objective. We present here the data obtained using RAPD analysis of 40 primers in 20 accessions of wild tetraploid emmer wheats (Triticum turgidum L. ssp. dicoccoides) and 10 genotypes of cultivated tetraploid durum wheats (Triticum turgidum L. ssp. durum) selected from geographically diverse locations. We have observed a higher level of polymorphism among different accessions of wild emmer wheat from Israel. Turkey, and Jordan than the group of cultivated American, Turkish, and Syrian durum wheats. These data have been used to generate a dendrogram suggesting the genetic relationships among these genotypes, and the most dissimilar genotypes are identified for future mapping and gene tagging work.

Base Sequence↗

PubMed2003

Monoamine oxidase A gene polymorphism, 5-HT 2A receptor gene polymorphism and incidence of nausea induced by fluvoxamine.

Selective serotonin reuptake inhibitors cause a side effect of nausea with high frequency, but there have been no accurate methods to predict its incidence. The authors first investigated whether a functional polymorphism in the monoamine oxidase A (MAOA-VNTR) and a -1438G/A polymorphism in the promoter region of the 5-HT(2A) gene were associated with the incidence of nausea induced by fluvoxamine. Fluvoxamine was administered for 6 weeks with a specific dosage plan (50-200 mg/day) in 66 Japanese major depressive patients. The frequency of MAOA-VNTR allele 1 was significantly higher in the patients without nausea than in ones with nausea in the statistical analysis including the patients whose plasma levels were below the average and who were considered to be pharmacodynamically more sensitive to nausea. This study showed that the genetic polymorphism of MAOA-VNTR might affect the incidence of nausea induced by SSRIs. If this finding is replicated in other studies with more subjects, MAOA-VNTR polymorphism would be of great clinical use to predict the incidence of nausea induced by SSRIs.

Adult↗

PubMed1984

Non-random association of the polymorphic Taq I restriction site, located 3 KB 5' to the human delta-globin gene, with the polymorphic Hind III sites within the G gamma- and A gamma-globin genes.

During the study of the DNA from 25 beta-thalassemic subjects from mediterranean origin the polymorphic Taq I restriction site located 3-kb 5' to the human delta-globin gene, was found non-randomly associated to the polymorphic Hind III sites within the G gamma- and A gamma-globin genes. This indicates that the 3' limit of the linkage group of polymorphic restriction sites including the gamma-globin genes is located downstream to the polymorphic Taq I site.

Base Sequence↗